Administration of ineffective anti-cancer therapy is associated with unnecessary toxicity and development of resistant clones. Indeed, each time cancer patients are treated, those individuals have a high chance of relapse and encounter a significant risk that their cancer may become more resistant to therapy. In this regard, attempts have been made over the years to develop an ex-vivo anti-cancer test that would provide clinically-relevant treatment information. However, due to the presence of cancer stem-like cell populations in a number of types of human cancer, which comprise only a small subset of the cancer cells within each cancerous tumor, but yet retain their stem cell properties of self-renewal and differentiate into phenotypically heterogeneous [4-12], aberrant progeny, an ex-vivo anti-cancer test capable of identifying treatment regimens that minimize toxicity and prevent the development of resistant clones has yet to be developed.
It has been observed that unlike the bulk of tumor cells, cancer stem-like cells frequently resist chemotherapy, and thereby cause a relapse of the disease [9, 10, 12]. Indeed, this resistance of the cancer stem-like cells can cause chemotherapeutic treatments to be ineffective and associated with unnecessarily high toxicity or the development of resistant clones. In certain types of cancer where neoplastic growth depends on cancer stem-like cells, it is thought that the eradication of the cancer stem-like cell population may be curative or may provide an effective complement to traditional treatment approaches such as surgery, chemotherapy, and/or radiation therapy. Presently, however, chemotherapeutic agent testing is still performed only on cancer cells from patients without prior separation and proliferation of the often chemotherapy-resistant cancer stem-like cells from the bulk cancer cells [39, 52-63]. Thus, there remains a need for a method that identifies an effective chemotherapeutic agent for a particular cancer that would eliminate both the cancer's bulk cancer cells and cancer stem-like cells. Such methods would be both highly desirable and beneficial for, among other things, cancer research and personalized anti-cancer treatments.